Lupeol and stigmasterol, major phytosterols in various herbal plants, possess anti-inflammatory activities and have been proposed as candidates for anti-cancer agents, but their molecular mechanisms are still unclear. Here, we investigated the effects of lupeol and stigmasterol on tumor and endothelial cells in vitro and their anti-cancer activities in vivo. Our results demonstrated that lupeol and stigmasterol suppressed cell viability, migration, and morphogenesis of human umbilical vein endothelial cells (HUVECs) but not cholangiocarcinoma (CCA) cells. Expression analyses showed that the treatment of both compounds significantly reduced the transcript level of tumor necrosis factor-α (TNF-α), and Western blot analyses further revealed a decrease in downstream effector levels of VEGFR-2 signaling, including phosphorylated forms of Src, Akt, PCL, and FAK, which were rescued by TNF-α treatment. In vivo, lupeol and stigmasterol disrupted tumor angiogenesis and reduced the growth of CCA tumor xenografts. Immunohistochemical analyses confirmed a decrease in CD31-positive vessel content and macrophage recruitment upon treatment. These findings indicate that lupeol and stigmasterol effectively target tumor endothelial cells and suppress CCA tumor growth by their anti-inflammatory activities and are attractive candidates for anti-cancer treatment of CCA tumors.

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Carbon dots (CDs) are fascinating nanomaterials with technologically relevant properties; however, the effects of heteroatom doping on several properties of CDs have not been studied. In this work, a facile method for the synthesis and heteroatom doping of carbon dots from table sugar was developed using nitric acid, phosphoric acid, and sulfuric acid as simultaneous catalysts and dopants. The optical properties, phenolic content, antioxidant activity, photostability, and cytotoxicity of the CDs were measured and compared. Lascorbic acid, a well-known antioxidant, and avobenzone and oxybenzone, common UV absorbers in sunscreens, were used for comparison. Interestingly, heteroatom doping has adverse effects on several properties of the CDs as the undoped CDs yielded the highest UV-vis absorption, phenolic content, antioxidant activity, photostability, and biocompatibility. Only fluorescence quantum yields were improved by heteroatom doping. These findings will be crucial for choosing precursors for the synthesis of CDs because heteroatoms inherently present in precursors can have negative effects on the properties of the resulting CDs.

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